Pharmacology Watch: GlaxoSmithKline Withdraws Lymerix: Company Cuts Losses’ on Controversial Lyme Disease Vaccine

Citing poor sales, GlaxoSmithKline has announced that it is withdrawing Lymerix, the Lyme disease vaccine, from the market. The vaccine was the first, and only, Lyme disease vaccine on the market. Lymerix generated $40 million in sales in 1999, its first year on the market, but sales have fallen steadily since. The vaccine has also been plagued by controversy regarding side effects claimed by patients—side effects that seem to mimic Lyme disease and include arthralgias, fatigue, and neurocognitive symptoms. The FDA reviewed a study of 10,000 patients (5000 active vaccine, 5000 placebo) and found no increase in side effects with the vaccine. But because of continued complaints by consumers, the Centers for Disease Control (CDC) independently reviewed more than 900 reported side effects. In a report issued in January, the CDC declared that the vaccine was not associated with unexpected events. Despite the report and statistics that show Lyme disease cases reaching record highs, Glaxo has decided to cut their losses and is pulling the vaccine from the market.

Measles Vaccine Weathers Storm in Europe

An outbreak of more than 600 cases of measles in Germany has been reported in the last few weeks. Most cases have occurred in Bavaria, an area that is known as a hotbed of opposition to the MMR vaccine. The German pediatricians report that only 80% of infants in Bavaria received the first dose of MMR and only 60% of children received the second dose in 2000. European opposition MMR has centered in England and Germany after early research linked the vaccine to autism. A soon-to-be-published English study also suggests that the measles virus is present in children with ileocolonic lymphodular hyperplasia, a variant of inflammatory bowel disease, and speculates that the source of the virus may be MMR. News of the data, which will be published in the April issue of Molecular Pathology, was broadcast on the BBC. The lay press in England and other European countries has run many related stories, which have fed the fears of parents that the vaccine causes more harm than benefit. This is complicated by the fact that hundreds of lawsuits are currently pending in England—lawsuits filed by parents who feel that their children have been harmed by the vaccine. Vaccine-phobia exists in the United States but is less pervasive, in part due to the work of the National Network for Immunization Information (NNII), which has helped disseminate useful information to parents and physicians regarding childhood immunizations. The organization has set up a new web site to provide an on-line clearinghouse for vaccine information. The web site, which is sponsored by several medical professional societies and has an impressive advisory board, can be found at www.immunizationinfo.org. The Network is a nonprofit and receives no financial support from the pharmaceutical industry. The web site has just added the recommended 2002 schedule for childhood immunizations. Changes for this year include recommendations for routine use of hepatitis B vaccine for all infants before hospital discharge, a schedule for catch-up vaccinations for children who are behind on routine immunizations, and recommendations for preadolescent assessment of the vaccine status. The site also offers a color-coded, easy-to-use schedule for all childhood immunizations.

Too Many Injections for Children?

The concern of most American parents regarding vaccines has more to do with the sheer volume of injections that children must endure. Current recommendations call for children to receive up to 20 shots before their second birthday. The antigen load from these vaccines has also led researchers to explore a possible link between vaccinations and the immune mediated diseases such as asthma and type I diabetes. The Institute of Medicine recently issued a report on this topic entitled "Immunization Safety Review: Multiple Immunizations and Immune Dysfunction." The report was issued by the Immunization Safety Review Committee of the Institute of Medicine, which was initially convened in 1991. The report found no relationship between immunizations and type I diabetes or an increased rate of various infections including pneumonia or meningitis. The evidence was inconclusive regarding a relationship between vaccines and asthma. Surprisingly, the report states that a child’s exposure to vaccine antigens is actually lower in 2002 than it has been in the past. This is due in part to the removal of the smallpox vaccine in 1971 and an improvement in the pertussis vaccine, which reduced the number of potential antigens 1000-fold. The report can be accessed at www.iom.edu. Another excellent review on this subject was published in the January issue of Pediatrics. Entitled "Addressing Parents Concerns: Do Multiple Vaccines Overwhelmed or Weaken the Infant’s Immune System?" (Pediatrics. 2002;109:124-129).

Cancer Vaccine Fast-Tracked by FDA

The US Food and Drug Administration has granted fast track status a novel cancer vaccine developed by Antigenics Inc. The vaccine is currently in phase III trials for the treatment of renal cell carcinoma. The fast track designation was awarded for the treatment of metastatic melanoma, which will begin phase III trials later this year. The drug, HSPPC-96 (trade name Oncophage) is a "personalized cancer vaccine." The process involves creating an antigenic "fingerprint" for each individual tumor, then designing a vaccine to sensitize the immune system to specific tumor antigens. The fast track designation is reserved for drugs to treat serious life-threatening conditions and for which there is no existing treatment. The designation virtually guarantees a priority review of the drug when phase III trials are completed.

Once Yearly Osteoporosis Treatments a Possibility

Women may soon be able to make a once yearly appointment to treat their osteoporosis. A recent study shows that an annual infusion of the bisphosphonate zoledronic acid is as effective as more frequent dosing for the treatment of osteoporosis. A yearly infusion of zoledronic acid also appears to be as effective as daily dosing of other bisphosphonates, such as alendronate or etidronate. The study, which was performed in Europe, New Zealand, and Canada, followed more than 350 postmenopausal women with low bone density. The women were randomized to placebo or intravenous zoledronic acid given in several dose regimens at 3-month intervals, 2 mg given every 6 months, or a single 4 mg dose administered once a year. At the end of 1 year, bone mineral density was assessed in the spine and the femoral neck. Increases in bone mineral density at both sites were found in all active medication groups and the increase was similar in all dosing schedules including the 4 mg once yearly group. The effect was also similar to published results with other oral bisphosphonates. The authors suggest that a once yearly infusion of zoledronic acid may eventually be a realistic alternative to oral bisphosphonates (and all their attendant side effects including esophagitis). This study is a phase II trial. (N Engl J Med. 2002;346:653-661). An FDA advisory board on oncologic drugs also recently recommended the approval of zoledronic acid for the treatment of bony metastases associated with a broad range of tumors including breast cancer in lung cancer. Novartis plans to market zoledronic acid under the trade name "Zometa."

Niacin and Statin Use Found to Raise HDL Cholesterol

Even low doses of niacin can effectively RAISE HDL cholesterol when used in conjunction with a statin, according to a recent study. Fifty patients who are stabilized on a statin were randomized to receive niacin 50 mg twice a day or placebo. The primary end points were change in HDL cholesterol and side effects such as flushing. The niacin patients had an increase in HDL cholesterol of 2.1 mg/dL, an increase that was statistically significant. Only 5 patients taking niacin noted flushing vs. 2 patients in the placebo group. There were no other significant side effects noted (Am Heart J. 2002;143:514-518). This study is important because traditional niacin therapy uses doses of 2000-3000 mg, doses that frequently result in intolerable side effects for many patients. Using low doses of niacin in conjunction with a statin safe and well-tolerated way to increase HDL cholesterol.